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Red pepper as a probe for obesity Obesity is epidemic; >30% of the U.S. population is now obese, about triple the rate in 1980. A staggering 70% of U.S. adults are considered either obese or overweight. Despite a widespread awareness of the problems that accompany obesity and an overwhelming popular preference to have a lean body mass index, most Americans do not have control over their weight. In the face of this problem, understanding the molecular underpinnings of obesity represents an important research goal. In JPR (DOI 10.1021/ pr901175w), Jong Won Yun and colleagues at Daegu University (Korea) used capsaicinsthe pungent component of red peppersto study protein expression in an animal obesity model. The researchers harnessed the ability of capsaicin to alter some of the protein-level effects of fat accumulation to afford new insights into obesity and identify potential biomarkers for possible treatments and further study. Fat is by no means a static body part. In mammals, excess nutrition is typically stored in white adipose tissue (WAT), a conglomeration of fat cells (adipocytes) that have a dynamic relationship with the surrounding body. WAT secretes cell-to-cell signals in the form of proteins called adipokines, and the fat molecules stored within each adipocyte are in a state of fluxscontinually added to by biosynthesis and depleted by release into the bloodstream. Although the balance of nutrition determines whether WAT grows or shrinks, turnover of the stored lipid molecules is constant. Brown adipose tissue (BAT) is the other major means of fat storage in mammals, and it has a specific purposesto provide heat in the absence of shivering. Hibernating animals, for example, lay down prodigious stores of BAT to generate warmth in
10.1021/pr100333u
the absence of kinetic activity. BAT adipocytes are loaded with mitochondria, which give BAT its brown color; these mitochondria can oxidize fat molecules within the cell to generate heat in the process called thermogenesis. Human newborns are endowed with significant BAT, but it is quickly depleted; little is thought to remain in
Hot molecule. Capsaicin, one of the “hottest” components of red pepper, made undesirable belly fat resemble a hibernating animal’s fat in some interesting ways when taken in a daily oral dose. By comparing rats on a highfat diet either with or without added capsaicin, researchers identified a number of proteins involved in the shift.
adults. WAT is thus what’s measured as “body fat percentage” in humanssand it’s an important organ in the human body, as even a highly muscular 180-pound male athlete will typically be estimated to carry >15 pounds of body fat. WAT isn’t merely a storage depot; it also serves as a regulator of energy metabolism throughout the body. An overabundance of WAT, however, can lead to dysregulation of adipokines, which is associated with problems such as diabetes, hypertension, and cardiovascular ailments, just to name a few. Yun’s group gave daily oral doses of capsaicin to rats fed a high-fat diet. “Capsaicin has been reported to increase thermogenesis,” explains Margriet Westerterp of Maastricht University (The Netherlands). “The increase is probably based on β-adrenergic stimulation.” So in a useful oversimplication,
© 2010 American Chemical Society
capsaicin might make WAT act more like BAT. The team divided young rats into three groups with differing diets: (i) normal rat chow with daily oral saline, (ii) a high-fat diet with daily oral capsaicin in saline, and (iii) a high-fat diet with daily oral saline. All three groups increased in weight as they grew, but in the order i < ii < iii. Capsaicin mitigated the weight gain from the high-fat diet by ∼ 8%. The researchers dissected the epididymal fat tissue, then used 2DE and MS to analyze protein expression in each group. Of >1000 spots visible on the gels, 10 proteins were found to be up-regulated and 10 down-regulated by capsaicin. Some surprises were in order. “The proteins are mostly associated with lipid metabolism and redox regulation,” says Yun. “There’s significant down-regulation of heat-shock protein 27 and Steap3 protein, and we show up-regulation of olfactory receptor [Olr1434] for the first time in association with obesity.” Edwin Mariman, also of Maastricht University, explains that “capsaicin is able to revert molecular processes induced by high-fat diet and at the same time stimulate processes increasing energy expenditureslike increasing PGC1a and UCP1 mRNA, indicating a higher number of mitochondria with a higher degree of uncoupling and thermogenesis.” In other words, “it suggests a phenotypic shift from WAT towards BAT.” Yun hopes the identified proteins “can be used for candidate marker proteins in the induction or suppression of obesity.” A longer term goal of “remodeling mature WAT into mitochondria-rich cells, with their high capacity for fatty acid oxidation, may be possible when treated with thermogenic compounds like capsaicin,” he adds. —Steven C. Powell
Journal of Proteome Research • Vol. 9, No. 6, 2010 2797
